Preparation and in vivo evaluation of surface heparinized small diameter tissue engineered vascular scaffolds of poly(ε-caprolactone) embedded with collagen suture

Abstract

Herein biodegradable poly(e-caprolactone) was electrospun into tubular microfibrous scaffolds and modified by the surface heparinization and wrapping of Type I collagen suture for enhancing anticoagulation activity and mechanical properties. The resulting scaffolds were featured by a double distribution of microfiber diameters ranged in 2.74 AE 0.44 and 5.15 AE 0.63 mm on the outer surface with tensile strength of 1.36 AE 0.37 MPa and Young's modulus of 8.31 AE 1.87 MPa. The burst pressure after embedded with collagen suture was increased to 2419 AE 121 mmHg, remarkably higher than that of the poly(e-caprolactone)-only scaffolds (1500 AE 136 mmHg) and native vessels. The scaffolds were evaluated in six rabbits for 20 weeks via a carotid artery interpositional model demonstrating a good patency. The effective cell infiltration, and rapid endothelialization and smooth muscle cell maturation were observed. There was no calcification in 20 weeks, and only one developed the aneurysm dilation after 16 weeks. It suggested that the surface heparinization is beneficial to improve the hydrophilicity and anticoagulation property of scaffolds, and embedment of collagen suture is useful to reinforce the mechanical properties and burst pressure.

Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

“…Heparin functionalization of synthetic small‐diameter TEVGs is an often‐reported strategy to prevent thrombus formation. [ 45–54 ] Surprisingly, we did not observe a clear reduction in platelet activation in the hep group when compared to bare group (Figure S3, Supporting Information). This observation, in case of heparin functionalized groups (either with or without IL‐4), is in apparent contrast with the canonical definition of heparin as a potent anticoagulant.…”

“…Several studies showed a positive effect of heparin functionalization of small‐diameter TEVGs on patency and tissue regeneration. [ 45–49,58,59 ] A recent example is a study by Matsuzaki et al., in which higher patency rates (85%) were reported for heparin‐eluting bilayered polycaprolactone/poly( l ‐lactide‐ co ‐caprolactone) (PCL‐PLCL) vascular grafts compared to non‐heparin grafts (20%) in carotid artery interposition replacement during 8 weeks follow‐up in sheep. [ 50 ] In contrast, other studies report adverse events with the heparin functionalization of small‐diameter TEVGs, with local formation of an α SMA‐rich neointimal layer in heparin functionalized grafts.…”

Hydrogel Complex Electrospun Scaffolds and Their Multiple Functions in In Situ Vascular Tissue Engineering

“…PCLH scaffold preparation was performed according to our previously published literature. ,, In short, PCL was dissolved in a DCM/methanol (volume ratio: 5:1) solution at a concentration of 0.2 g/mL. The electrospinning parameters were set as follows: a voltage of 15 kV, receive distance of 17 cm, and injection rate of 3 mL/h to obtain a tubular PCL scaffold.…”

“…The structure and function of regenerated blood vessel were similar to those of the native aorta after three months, showing the promising potential of in situ VTE. We also prepared small-diameter heparin-modified PCL (PCLH) scaffolds by electrospinning and directly implanting them into animal models including rats, rabbits, and canines according to the concept of in situ VTE. − The PCLH scaffold can maintain long-term in vivo patency . However, a high aneurysm incidence was observed in all animal models (4/10 in rats, 1/1 in canines, and 4/6 in rabbits), which negatively impacts the success of VTE grafts.…”

“…Thus, precautionary measures must be taken to decrease the aneurysm incidence before this scaffold can be tested with clinical trials. Traditionally, some physical measures, including wrapping the scaffold with bio-absorbable sutures or increasing the thickness of the scaffold wall, can be adopted to strengthen the scaffold . However, these physical measures are mainly focused on strengthening the scaffolds, but aneurysm occurrence is due not only to the poor mechanical properties of the scaffold but also to the slow vascular regeneration rate, which cannot replace the role of the scaffold and provide sufficient mechanical strength. , On the other hand, it should be noted that the scaffold for ideal in situ VTE should be able to conduct better vascular regeneration in vivo since it omits the in vitro cell culture procedure.…”